Social environment elicits lateralized navigational paths in two populations of typically developing children

The current study provides the first evidence of human lateralized navigation of a social space within a naturalistic environment. We employed a quantitative, observational approach and report on a detailed set of nearly 700 independent navigational routes from two separate child populations consisting of over 300 typically developing children, aged five to fourteen years. The navigational path was considered across the sagittal plane (left, right) around three distinct target types (peer, adult and object). Both child populations expressed a significant bias for choosing a rightward navigational path around a human tar- get (e.g. peer, adult) and no lateral preference for navigation around fixed, inanimate objects. A rightward navigational path provides an advantage for the left visual field and the right hemisphere, facilitating both the production and perception of social-emotion stimuli. The findings are consistent with evidence from studies of non-human animal species demonstrating that the social environment elicits predictable lateralized behavior, and support an early evolutionary delineation of functional processing by the two hemispheres

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies

Donor template delivery by recombinant adeno-associated virus for the production of knock-in mice

Abstract Background The ability of recombinant adeno-associated virus to transduce preimplantation mouse embryos has led to the use of this delivery method for the production of genetically altered knock-in mice via CRISPR-Cas9. The potential exists for this method to simplify the production and extend the types of alleles that can be generated directly in the zygote, obviating the need for manipulations of the mouse genome via the embryonic stem cell route. Results We present the production data from a total of 13 genetically altered knock-in mouse models generated using CRISPR-Cas9 electroporation of zygotes and delivery of donor repair templates via transduction with recombinant adeno-associated virus. We explore the efficiency of gene targeting at a total of 12 independent genetic loci and explore the effects of allele complexity and introduce strategies for efficient identification of founder animals. In addition, we investigate the reliability of germline transmission of the engineered allele from founder mice generated using this methodology. By comparing our production data against genetically altered knock-in mice generated via gene targeting in embryonic stem cells and their microinjection into blastocysts, we assess the animal cost of the two methods. Conclusions Our results confirm that recombinant adeno-associated virus transduction of zygotes provides a robust and effective delivery route for donor templates for the production of knock-in mice, across a range of insertion sizes (0.9–4.7 kb). We find that the animal cost of this method is considerably less than generating knock-in models via embryonic stem cells and thus constitutes a considerable 3Rs reduction

Additional file 1 of Donor template delivery by recombinant adeno-associated virus for the production of knock-in mice

Additional file 1: Table S1 - Production details for all of the individual embryo manipulation sessions. Table S2 - Production details per allele generated, listed by titre of rAAV used. Table S3 - Production data for embryo survival and birth rate following delivery by electroporation and pronuclear microinjection, used for the preparation of Fig. 2. Table S4 - Animal use dataset used for the presentation of Fig. 6. Table S5 - Genotyping primers, qPCR assays, CRISPR sgRNA target sequences and construct details

Additional file 1: of eQTL discovery and their association with severe equine asthma in European Warmblood horses

Figure S1. Minimum D-statistics determine mean read count cutoffs. Figure S2. PCA plots of normalized variance stabilized RNAseq counts after KS test filter. Figure S3. PCA plots of 1,056,195 SNP genotypes and colored by cohort. Figure S4. Matrix eQTL histograms and QQ-plots for all p-values for all cis and trans eQTL analyses using tag SNPs for the MCK1 treatment. Figure S5. Low confidence cis eQTLs. Figure S6. Joint modeling with eQTLBMA with possible overestimation of shared eQTLs across all PBMC treatments. Figure S7. Distance between eSNPs with the lowest FDR values per gene is small. Figure S8.. Enrichment of SNPs in trans regulatory hotspots genome wide. Figure S9. GWAS for RAO. Figure S10. Loss of DEXI gene expression regulation in HDE. Figure S11. Cis trans eQTL plot for all eQTLs for treatment HDE9. Table S1. High confidence additive linear cis eQTLs from the MCK treatment. Table S2. Low confidence additive linear cis eQTLs from the MCK treatment. Table S3. High confidence additive linear trans eQTLs from the MCK treatment. Table S4. Low confidence additive linear trans eQTLs from the MCK treatment. Table S5. High confidence additive linear cis eQTLs from the LPS treatment. Table S6. Low confidence additive linear cis eQTLs from the LPS treatment. Table S7. High confidence additive linear trans eQTLs from the LPS treatment. Table S8. Low confidence additive linear trans eQTLs from the LPS treatment. Table S9. High confidence additive linear cis eQTLs from the RCA treatment. Table S10. Low confidence additive linear cis eQTLs from the RCA treatment. Table S11. High confidence additive linear trans eQTLs from the RCA treatment. The eQTLs reported are limited to one eQTL per gene, representing the eSNP with the lowest FDR value for each gene. Table S12. Low confidence additive linear trans eQTLs from the RCA treatment. Table S13. High confidence additive linear cis eQTLs from the HDE treatment. Table S14. Low confidence additive linear cis eQTLs from the HDE treatment. Table S15. High confidence additive linear trans eQTLs from the HDE treatment. Table S16. Low confidence additive linear trans eQTLs from the HDE treatment. Table S17. Two proportion z-test calculation. Table S18. 4157 significant eQTLs discovered with eQTLBMA. Table S19. Trans eQTL results for the trans regulatory hotspot on chromosome 11 (SNP MNEc.2.11.60892596.PC). Table S20. Trans eQTL results for the trans regulatory hotspot on chromosome 13 (SNP MNEc.2.13.18333037.PC). Table S21. Panther gene enrichment GO process results for genes regulated by the trans regulatory hotpot on chromosome 11 (MNEc.2.11.60892596.PC). Table S22. Panther gene enrichment GO process results for genes regulated by the trans regulatory hotpot on chromosome 13 (MNEc.2.13.18333037.PC). Table S23. GWAS results. Table S24. All significant cis eQTLs for the MCK treatment. Table S25. All significant cis eQTLs for the LPS treatment. Table S26. All significant cis eQTLs for the RCA treatment. Table S27. All significant cis eQTLs for the HDE treatment. Table S28. Linkage disequilibrium and allele frequencies between RAO associated SNPs on chromosome 13 positions 32,843,309 – 33,502,488. Table S29. Sample information for 82 individuals used in eQTL analyses. Table S30. Sample information for all 379 individuals. (ZIP 51963 kb